Interleukin-17 (IL-17) producing T helper cells (Th) are critical to maintaining gut barrier integrity and host response against extracellular bacterial and fungal infections. During the course of Simian Immunodeficiency Virus (SIV) infection, Th17 cells that express C-C chemokine receptor 6 (CCR6) are rapidly and preferentially depleted from mucosal tissues. It has been proposed that CCR6+ Th17 cells are more permissive to SIV, and are thus, preferentially infected.
Lymphocytes from Peripheral Blood Mononuclear Cells (PBMC), spleen, and Mesenteric Lymph Nodes (MLN) of SIV+, viremic rhesus macaques were isolated and simulated for 6 hours with PMA and ionomycin in the presence of Brefeldin A. CD28+ memory CD4 T cells were studied and CCR6+/IL-17+ and IL-17- CD4 T cells (Th17 cells), CCR4-/IFNg+ and IFNg- CD4 T cells (Th1 cells), CCR4+/IFNg-/IL-17- CD4 T cells (Th2 cells) and FoxP3+ CD4 T cells (Tregs) were then flow cytometrically isolated, and the proportions of cells harboring SIV DNA were then assessed through qPCR.
Viral DNA was detected in all subsets of memory CD4 T cells (irrespective of functionality, phenotype, or anatomic location). However, irrespective of anatomic site studied, we found that no one population of isolated memory, CD28+, CD4 T cells harbored more (or less) viral DNA than any other population of memory CD4 T cells.
Loss of CD4 T cells is a hallmark of progressive HIV/SIV infection and several studies have shown that Th17 cells are preferentially loss from mucosal tissues and lymph nodes that drain mucosal tissues. From our data it is unlikely that preferential loss of Th17 cells is attributed to preferential infection by the virus, itself.